The mechanisms of cellular lesions induced by lung ischemia and reperfusion are not fully understood and, in particular, the consequences of pulmonary ischemia and reperfusion injury on mitochondrial ... [more ▼]

The mechanisms of cellular lesions induced by lung ischemia and reperfusion are not fully understood and, in particular, the consequences of pulmonary ischemia and reperfusion injury on mitochondrial function have not been previously investigated. Therefore, we studied the respiratory function of isolated pulmonary mitochondria in a swine model of lung ischemia and reperfusion. We demonstrated that prolonged hypothermic (4 degrees C) ischemia induces significant lesions of the mitochondrial respiratory chain, particularly if ischemia is followed by normothermic reperfusion. These results should be integrated in the cellular alterations induced by the ischemia-reperfusion injury. In another swine model mimicking controlled non-heart beating donors, we demonstrated that thirty minutes of cardiac arrest do not promote significant alteration of the mitochondrial respiratory function. In contrast, forty-five minutes of cardiac arrest, induced significant mitochondrial lesions. This pulmonary tolerance to normothermic cardiac arrest might be explained by the presence of air in the lung airways, allowing some aerobic metabolism after circulatory arrest. These results suggested that lung grafts might be harvested from non-heart beating donors after thirty minutes of cardiac arrest, significantly increasing the pulmonary graft pool. [less ▲]

BACKGROUND: Platelet count and function are particularly damaged by cardiopulmonary bypass (CPB). This study evaluated the effects of a novel CPB circuit in terms of platelet count and activation, and ... [more ▼]

BACKGROUND: Platelet count and function are particularly damaged by cardiopulmonary bypass (CPB). This study evaluated the effects of a novel CPB circuit in terms of platelet count and activation, and postoperative need for blood products. METHODS: One hundred patients undergoing coronary grafting were randomized in two groups: control group (n = 50) and test group (n = 50, surface modifying additives circuit, SMA group). Blood samples were taken before, during, and after CPB. Postoperative blood loss, number of transfused blood products, and postoperative variables were recorded. RESULTS: The platelet count decreased less in the SMA group compared to the control group (end of CPB: respectively, 165 +/- 9 x 10(3)/mm3 vs 137 +/- 8 x 10(3)/mm3; p < 0.01). This was paralleled by a reduction in beta-thromboglobulin plasma levels in the SMA group. There was a trend to decreased blood loss in the SMA group, but the difference was significant only in patients taking aspirin preoperatively (p < 0.05). In the SMA group nearly 50% less fresh frozen plasma and platelet units were administered (p < 0.01). No operative deaths were observed. CONCLUSIONS: The use of circuits with surface additives is clinically safe, preserves platelet levels, and attenuates platelet activation. This may lead to a reduced need for blood products. [less ▲]

BACKGROUND: Cardiopulmonary bypass (CPB) initiates a whole-body inflammatory response where complement and neutrophil activation and cytokine release play an important role. This prospective trial examined the effects of both heparin-coated circuits and aprotinin on the inflammatory processes during CPB, with respect to cytokine release and neutrophil activation. METHODS: Two hundred patients undergoing cardiac surgery were randomized in four groups of 50 patients each: heparin-coated circuit with aprotinin (HCO-A) or without aprotinin (HCO) administration, and uncoated circuit with aprotinin (C-A) or without aprotinin administration (C). In groups receiving aprotinin, a high-dose regimen was given. In all groups, high initial doses of heparin were used (3 mg/kg intravenously). Tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and IL-8, and myeloperoxidase and elastase levels were measured in plasma samples taken before, during, and after CPB. RESULTS: In all groups, the TNF-alpha, IL-6, and IL-8 levels reached a maximum after protamine administration. After 24 hours, they remained significantly elevated (IL-6 and IL-8) or returned to baseline values (TNF-alpha). A similar pattern was observed with myeloperoxidase and elastase levels. No significant intergroup differences were observed. CONCLUSIONS: CPB is associated with cytokine release and neutrophil activation, which are not attenuated by the use of heparin-coated circuits or by the administration of aprotinin. Aprotinin and heparin-coated circuits do not show additive effects. [less ▲]

Antioxidant status and titers of autoantibodies against oxidized low-density lipoproteins (ox-LDL-Ab) were investigated in top soccer (S; n = 21, age 24.6 +/- 4.3 years) and basketball (B; n 3,000 mIU/ml) in ox-LDL-Ab were found in half the players (12S and 4B) with a maximum reaching 6000 mIU/ml (normal range: 200-600 mIU/ml), showing an in vivo LDL oxidation. There was no correlation between ox-LDL-Ab titers and chlolesterol, LDL cholesterol, or antioxidant levels. Nevertheless, plasma vitamin C concentration was lower in athletes having high levels of ox-LDL-Ab when compared with those with normal levels (8.49 +/- 3.14 mirogram/ml vs. 10.39 +/- 2.55 microgram/ml), but this difference was not statistically significant. In conclusion, our data suggest that potential atherogenic and cardiovascular risks as reflected by high titers in ox-LDL-Ab may exist in some top athletes despite a nonaltered antioxidant status. [less ▲]

A large number of epidemiological and clinical studies suggest that oxidative stress plays an important role in the development of cardiovascular diseases. In this way, following reference values in ... [more ▼]

A large number of epidemiological and clinical studies suggest that oxidative stress plays an important role in the development of cardiovascular diseases. In this way, following reference values in plasmatic antioxidants have been determined in a group of 123 blood donors (94 males, 29 females; age: 21-64 years) living in the surroundings of Liege, Belgium: vitamin A (1.5-3.62 mmol/l), vitamin C (3.68-75.21 mmol/l), vitamin E (16.98-46.46 mmol/l), ratio vitamin E/cholesterol (3.92-8.32 mmol/mmol), selenium (0.66-1.26 mmol/l), sulphydryl proteins (216-556 mmol/l), uric acid (174-477 mmol/l), superoxide dismutase (542-852 IU/g hemoglobine), glutathion peroxidase (39.55-91.83 IU/g hemoglobine). Only a few number of subjects were found with values corresponding to high risk of deficiency in antioxidants although low values in vitamin C (< 11.35 mmol/l) and in selenium (< 0.75 mmol/l) were respectively observed in 5.69 and 10.5% of our subjects. Autoantibodies against oxidized LDL, as marker of oxidative stress, and homocysteine, as a risk factor of atherosclerosis involved in the development of oxidative stress, have also been investigated. Approximatively 40% of the population presented values higher than the superior limit mean value (20.3% > 650 IU/l in autoantibodies and 19.5% > 15.2 mmol/l in homocysteine) that are, however, not correlated with age or low levels in antioxidants. The effect of smoking (25% of the population) contributed to significantly decrease vitamin C, selenium and glutathion peroxidase concentrations by 31.9 and 13% when compared to nonsmokers. Intake of 1 to 4 fruits per day resulted in a significant increase of 56.9% in vitamin C when compared to nonconsumers (26.8% of the population). In contrast, homocysteine concentrations were significantly decreased by 21.4% in fruits consumers. Thank to the development of methods allowing the routine dosage of all these parameters, general practitioners can now easily establish the oxidative stress status of their patients and, as fonction of getting patterns, detect populations at risk of developing cardiovascular diseases. [less ▲]

BACKGROUND: The aim of this study was to compare the effects of Euro-Collins and University of Wisconsin solutions on pulmonary mitochondrial function after cold ischemia and subsequent warm reperfusion ... [more ▼]

BACKGROUND: The aim of this study was to compare the effects of Euro-Collins and University of Wisconsin solutions on pulmonary mitochondrial function after cold ischemia and subsequent warm reperfusion. METHODS: Seventeen pigs underwent lung harvesting after classical lung flush with either University of Wisconsin or Euro-Collins solutions. The mitochondria were isolated from fresh swine lungs, from swine lungs subjected to 24 hr of cold ischemia, and from swine lungs subjected to 24 hr of ischemia followed by 30 min of subsequent ex vivo reperfusion at 37 degrees C with Krebs-Henseleit buffer solution and air ventilation. Mitochondrial oxidative phosphorylation parameters were determined in isolated mitochondria by in vitro measurement of oxygen consumption rates. During reperfusion, the lung function was assessed by the pulmonary aerodynamic parameters and the pulmonary vascular resistance. RESULTS: Relative to controls, mitochondria submitted to cold ischemia showed an alteration in the oxidoreductase activities of the respiratory chain. However, the yield of oxidative phosphorylation was conserved. After reperfusion, pulmonary mitochondria underwent a significant worsening in the oxidoreductase activities of the respiratory chain, and a decrease in the respiratory control and the efficiency of oxidative phosphorylation. Meanwhile, the reperfused lungs showed evidence of early dysfunction, assessed by the aerodynamic parameters and pulmonary vascular resistance. In this model, there was no advantage of University of Wisconsin solution over Euro-Collins solution. CONCLUSIONS: The mild mitochondrial alterations after cold ischemia were not sufficient to explain the limited tolerance of lung to ischemia. After reperfusion, the mitochondrial damage was more severe and could be involved in the posttransplant lung dysfunction. [less ▲]

in Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery and International Society For Cardiovascular Surgery, North American Chapter (1997), 26(2), 346-50

Controlled limb reperfusion was performed in two patients who were admitted for lower limb-threatening ischemia as a result of embolism. After embolectomy, the inflow blood was drained with a cannula and ... [more ▼]

Controlled limb reperfusion was performed in two patients who were admitted for lower limb-threatening ischemia as a result of embolism. After embolectomy, the inflow blood was drained with a cannula and mixed with a crystalloid solution to obtain an hyperosmolar, hypocalcemic, alkalotic, and substrate-enriched (aspartate, glutamate) reperfusate. This reperfusate was reinjected with a roller pump for 30 minutes through two cannulas inserted in the profunda and superficial femoral arteries. Temperature, intraarterial pressures, and flow were closely controlled. No complications occurred, and complete recovery of motor and sensory functions were observed, with restoration of pedal pulses. [less ▲]

In control rabbits, a renal ischemia of 60 min followed by 10 min of reperfusion resulted in an enhanced free radical production in cortical tissue, as assessed by a significant decrease of free ... [more ▼]

In control rabbits, a renal ischemia of 60 min followed by 10 min of reperfusion resulted in an enhanced free radical production in cortical tissue, as assessed by a significant decrease of free glutathione (42%), protein-bound GSH (17%), and vitamin E (49%). In contrast, catalase or glutathione peroxidase activities were not affected by these experimental conditions. Free radical production in this model was also measured directly using electron spin resonance (ESR) spectroscopy associated with a PBN (alpha-phenyl N-tert-butyl-nitrone) spin trap agent in the venous blood arising from the ischemic kidney. The signal consisted of a triplet of doublets. In contrast, no signal could be detected in control blood samples taken prior to inducing ischemia. The burst of free radical production occurred in the early phase after restoration of flow in the kidneys rendered ischemic, as evidenced by a signal of weak intensity which generally appeared within the third minute after reperfusion and progressively increased to form a well-defined asymmetric signal following 10 min of reperfusion. The precise nature of free radicals trapped by the PBN agent remains, however, to be elucidated, but analysis of the coupling constants (aN = 14.5-15 G; a beta H = 2.5-3 G) and asymmetry of the central doublets suggests that the ESR signal may arise from a nitorxy-radical adduct resulting from the spin trapping by PBN of both oxygen- or carbon-centered radicals of lipid origin. As evidenced by both direct and indirect measurements, exchange of rabbit blood immediately after inducing renal ischemia with 30 ml/kg of Diaspirin Crosslinked Hemoglobin (7.5 g/dl in lactated electrolyte) or human serum albumin (7.5 g/dl in lactated electrolyte) did not exacerbate free radical production mediated by an ischemia reperfusion phenomenon, a typical situation found in a resuscitation setting. [less ▲]

According to a recent hypothesis suggesting the potential role of free radical formation in the clozapine-induced agranulocytosis, we have evaluated the susceptibility to the peroxidase-mediated oxidation ... [more ▼]

According to a recent hypothesis suggesting the potential role of free radical formation in the clozapine-induced agranulocytosis, we have evaluated the susceptibility to the peroxidase-mediated oxidation of different dibenzazepine analogues. On the one hand, compounds with an arylamine group such as clozapine or isoclozapine present a high reactivity in the horseradish peroxidase or myeloperoxidase systems and, on the other hand, fluperlapine, though known to induce agranulocytosis, and other dibenzothiazepine and dibenzoxazepine derivatives appear insensitive to oxidation. Consequently, among tricyclic derivatives, the way of diaryloxa- and diarylthiazepine compounds could be an alternative for the development of safer drugs such as antipsychotics. [less ▲]

An increasing body of data suggest that strenuous exercise triggers an inflammatory response having some similarity with those occurring in sepsis. Indices of this inflammatory response to exercise (IRE ... [more ▼]

An increasing body of data suggest that strenuous exercise triggers an inflammatory response having some similarity with those occurring in sepsis. Indices of this inflammatory response to exercise (IRE) especially include leukocytosis, release of inflammatory mediators and acute phase reactants, tissue damage, priming of various white blood cell lines, production of free radicals; activation of complement, coagulation and fibrinolytic cascades. Inflammatory responses to strenuous exercise and sepsis could in part be due to the release of endotoxin in blood as common triggering factor, but it seems that tissue damage and/or contact system activation are more important triggering mechanisms in exercising subjects. While the magnitude and duration of cellular and humoral changes associated with IRE are quite different from those observed in sepsis, recent human studies suggested that chronic and/or excessive IRE could have adverse effects. Among the possible consequences of acute and chronic IRE are delayed onset muscular soreness and loss of force, cardiovascular complications, intravascular hemolysis, hypoferraemia and increased susceptibility to infection. [less ▲]

in Canadian Journal of Veterinary Research = Revue Canadienne de Recherche Vétérinaire (1994), 58(4), 309-12

This preliminary study demonstrated the existence of a free radical generation during an experimental postischemic muscular reperfusion in a halothane anesthetized horse. The authors used alpha-phenyl-N ... [more ▼]

This preliminary study demonstrated the existence of a free radical generation during an experimental postischemic muscular reperfusion in a halothane anesthetized horse. The authors used alpha-phenyl-N-tert-butylnitrone as a spin trap agent and the electronic paramagnetic resonance method to observe in vivo a free radical generation. [less ▲]

Treatment of suprarenal aneurysms and renal artery reconstructions are both responsible for normothermic ischemia of the kidney (during clamping) followed by reperfusion (declamping). During reflow ... [more ▼]

Treatment of suprarenal aneurysms and renal artery reconstructions are both responsible for normothermic ischemia of the kidney (during clamping) followed by reperfusion (declamping). During reflow through an organ undergoing ischemia the production of free radicals can be associated with cell injury and a no-reflow phenomenon characterized by perfusion defects after a period of transient hyperemia. The objectives of this study were to demonstrate the existence of this phenomenon in the kidney undergoing ischemia followed by reperfusion and to test the potential protection afforded by an iron chelator (desferrioxamine) since free radical reactions are catalyzed by iron. Adult New Zealand white rabbits were divided into the following three groups: group A, 15 minutes of ischemia plus 10 minutes of reperfusion; group B, 60 minutes of ischemia plus 10 minutes of reperfusion; and group C, 60 minutes of ischemia plus 10 minutes of reperfusion combined with infusion of desferrioxamine (50 mg/kg). Cortical microcirculation in the kidney was measured by laser Doppler flowmeter before ischemia and 1, 5, and 10 minutes after reperfusion. Vitamin E content was determined in the cortex of the left kidney after 10 minutes of reperfusion and compared with that of the right (control) kidney. After 1 minute of reperfusion the cortical microcirculatory flow was significantly increased in all three groups (reactive hyperemia). In groups A and C blood flow returned to preclamping values after 10 minutes of reperfusion; however, blood flow in group B remained significantly reduced (29.2% +/- 10.5%) after 5 minutes of reperfusion with a further reduction to 48.5% +/- 5.7% after 10 minutes. These findings were correlated with the dosage of vitamin E since the vitamin E content was greatly reduced by 46.7% +/- 7.8% in group B but did not change significantly in groups A and C. This study shows that 60 minutes of normothermic ischemia is followed by a significant reduction in cortical microcirculatory flow (no-reflow phenomenon). Infusion of an iron chelator (desferrioxamine), however, which decreases the intensity of lipid peroxidation induced by the free radicals, preserves the microcirculatory flow. [less ▲]

After surgical renal revascularisation, warm renal ischaemia due to renal artery cross-clamping contributes to postoperative renal dysfunction. After reperfusion, free radicals are thought to be a ... [more ▼]

After surgical renal revascularisation, warm renal ischaemia due to renal artery cross-clamping contributes to postoperative renal dysfunction. After reperfusion, free radicals are thought to be a significant cause of injury. Nevertheless, indisputable proof of free radical production is scarce, partly because of their transient nature. In this study, electron paramagnetic resonance and vitamin E levels were used to demonstrate the free radical production after renal ischaemia and reperfusion. Rabbit kidneys were submitted either to 15 or 60 minutes of ischaemia followed by reperfusion. A spin trap agent (alpha-phenyl-N-tert-butyl nitrone (PBN), 20mg/ml, 1 ml/min) was infused during reperfusion directly into the left renal artery via an aortic catheter before declamping. Blood samples were selectively drawn from the left renal vein for ESR analysis (Varian spectrometer E109) of lipidic residues extracted from blood samples. The vitamin E content of the left renal cortex was determined by HPLC procedure. The right renal cortex was used as a control for the vitamin E values. In the venous effluent, ESR analysis revealed the formation of a spectrum consisting of a triplet of asymmetric doublets. This signal resulted from the spin trapping by PBN of a mixture of both oxygen- and carbon- centred lipidic radicals. The amplitude of the signal which is proportional to the amount of free radicals was significantly higher after 60 minutes ischaemia than after 15 minutes.(ABSTRACT TRUNCATED AT 250 WORDS) [less ▲]